Journal article
Characterization of epidermal growth factor receptor mutations in non-small-cell lung cancer patients of African-American ancestry
Oncogene, v 30(15), pp 1744-1752
14 Apr 2011
PMID: 21132006
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Epidermal growth factor receptor (EGFR) mutations are predictive markers for response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC). The most common mutations, exon 19 short deletions and exon 20 point mutation (L858R), activate the tyrosine kinase and confer sensitivity to EGFR-TKIs. However, the function and sensitivity of rare mutations to EGFR-TKIs are unknown. In this study, we found five EGFR mutations out of 16 patients with NSCLC of African-American descent. The frequency of such mutations in this patient population appears to be significantly higher than previously reported. Two of them (N771GY and A767-V769dup) are rare insertion mutations located in exon 20. Using YFP-tagged EGFR mutants, we demonstrated that the mutations confer increased kinase activity, but no sensitivity to erlotinib at clinically available concentrations. In addition, we examined efficacy of PF00299804, an irreversible EGFR-TKI. Although the drug failed to show efficacy to T790M and S768N mutations, the exon 20 insertion mutations were sensitive to PF00299804. These data suggest that rare mutations in exon 20 are resistant to erlotinib but may be sensitive to irreversible inhibitors.
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Details
- Title
- Characterization of epidermal growth factor receptor mutations in non-small-cell lung cancer patients of African-American ancestry
- Creators
- T Harada - National Institutes of HealthA Lopez-Chavez - National Institutes of HealthL Xi - National Institutes of HealthM Raffeld - National Institutes of HealthY Wang - National Institutes of HealthG Giaccone - National Institutes of Health
- Publication Details
- Oncogene, v 30(15), pp 1744-1752
- Publisher
- Nature Publishing Group UK
- Number of pages
- 9
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000289512200002
- Scopus ID
- 2-s2.0-79954574430
- Other Identifier
- 991022059860004721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology